Our previous work has suggested the hepatic metabolism of aldosterone to its polar metabolites to be of major importance in the mechanism of action of aldosterone. We have demonstrated in plasma of male rats, during the latent period of the hormone, at least five unidentified polar metabolites of aldosterone. The quantities of polar metabolites present in the plasma and kidney have been correlated with the magnitude of the antinatriuretic and kaliuretic renal responses to aldosterone. Synthesis of these metabolites in the liver may (a) account for part of the latent period of aldosterone and (b) be necessary such that appropriate levels of these metabolites be attained in the plasma and kidney to regulate the extent of individual renal electrolyte effects. Dietary intake of sodium and potassium, sprironolactone, gonadal and pituitary hormones, have all been demonstrated to alter hepatic metabolism of aldosterone in rats. The objective of the proposed work is to investigate the effect of these cationic, antimineralocorticoid, and hormonal regulatory influences on (a) the rates of excretion of aldosterone metabolites and conjugates via the bile, (b) the extent of the enterohepatic circulation of aldosterone and its metabolites, and importantly (c) the concentration of aldosterone and the composition of its metabolites attained in the plasma and kidney during the latent period and (d) the in vitro synthesis of the individual metabolites of aldosterone using slices and subcellualr fractions of liver. The in vitro synthesis of these polar metabolites will provide sufficient quantities for both their chemical identification using G.C.-Mass Spec. and for testing their mineralocorticold activity. It is of key importance to determine the mechanisms by which these factors regulate the synthesis in the liver and concentrations of the individual polar metabolites of aldosterone in plasma and kidney. Correlation of the appearance in the plasma and kidney of appropriate concentrations of individual metabolites of aldosterone with known physiological responses to aldosterone in the kidney under such conditions, will be important in determining the physiological importance of the hepatic metabolism of aldosterone and the mechanism of its action.